This invention relates generally to components of a diagnostic apparatus, and more particularly to an improved biosensor having a lens (xe2x80x9cwaveguidexe2x80x9d) and associated flow cell.
International Application No. PCT/US94/05567 (International Publication No. 94/27137, published Nov. 24, 1994) to the University of Utah Research Foundation discloses an apparatus for multi-analyte homogeneous fluoroimmunoassays. In one embodiment, the application discloses an apparatus which uses a biosensor having a planar waveguide sandwiched, with an associated gasket, between two plates (FIGS. 3A-3C of Internat""l Publ. No. 94/27137). The inner edges of the gaskets serve as walls for a reaction reservoir or well. Fluorescence-emitting tracer molecules are bound to the waveguide surface and are excited by an evanescent field penetrating into the adjacent solution from a light beam propagated within the waveguide, the beam being introduced at, for example, a front end of the waveguide. In the reaction reservoir, a liquid (e.g., serum or blood) is introduced and is allowed to admix with capture molecules associated with the waveguide surface (e.g., by xe2x80x9ccoating chemistryxe2x80x9d as disclosed on pages 32 to 33 of the international application). The emitted fluorescence is then directly collected from the zone of evanescent penetration. In one particular embodiment, the biosensor has transparent walls which define the reservoirs. (E.g., FIGS. 11A-C of Internatl. Publn. No. 94/27137). The application also discloses integrally formed or molded biosensors. (E.g., FIGS. 12A, 12B and 13 of Internatl. Publn. No. 94/27137).
Unfortunately, the waveguide portion of integrally formed or molded biosensors may exhibit deformation upon fabrication, or warping during storage or temperature changes. Also, gaskets may not reliably seal or are not always sufficiently inert to reactants, and thus may interfere with the desired analysis.
It would be desirable to have a biosensor having reservoirs with inert walls, the walls being readily detachable from the waveguide so that one waveguide could be readily exchanged for another.
The invention includes a biosensor with a reservoir or reservoirs, the biosensor including a waveguide placed (e.g., xe2x80x9csandwichedxe2x80x9d) between a plurality of members such as plates, at least one of the members being formed to define the walls of the reservoir or reservoirs where the reaction to be analyzed takes place. The reservoir walls are preferably an inert, opaque material such as a passivated metal (e.g., black anodized aluminum). Although the biosensor may include a gasket, the gasket is associated with the plurality of members and waveguide in such a way (e.g., by recessing the gasket into a channel formed into a metal plate) so that the gasket does not form any significant portion of the reservoir wall. Waveguides of varying composition (e.g., plastic, quartz, glass or siliconoxynitride) may be associated with the members to form the biosensor. A lens or lenses may be integrated with the waveguide. The metal plate of the biosensor has input and output ports for infusing, draining, or oscillating the liquid to be analyzed in the reaction reservoir.
Due to the sandwiching of the waveguide in between the members, the planar waveguide is generally less distorted than that of an integrally formed biosensor. A reaction to be analyzed is not interfered with due to the use of opaque, inert metal to structurally define the reservoir.
The biosensor design is advantageously configured to interact with a flat waveguide having a rear integrated lens design for reading light passing through the waveguide (not fluorescent/evanescent light, but reading the core laser beam light) to monitor coupling efficiency and beam quality. The invention thus also includes a flat waveguide associated with a rear lens to couple light out of the waveguide (and a biosensor using such a lens) to serve as a quality control measure, thus insuring that the biosensor is properly placed and that the light source is working.
The invention also includes orienting the biosensor in a particular position relative to an optical reading device and laser which increases the performance of the biosensor to the point where, surprisingly, whole blood can be quickly analyzed.